-
1.
An updated systematic review and meta-analysis of the effect of statins on asymmetric dimethylarginine.
Zinellu, A, Mangoni, AA
Nitric oxide : biology and chemistry. 2022;:26-37
Abstract
OBJECTIVES We conducted an updated systematic review and meta-analysis of the effect of statins on serum or plasma concentrations of the endogenous inhibitor of endothelial nitric oxide synthase, asymmetric NG,NG-dimethyl-l-arginine (ADMA). METHODS A systematic literature search was conducted in the electronic databases PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively. RESULTS In 23 studies, reporting 25 treatment arms in 845 participants (mean age 53 years, 57% males, treatment duration 4-48 weeks), statins significantly reduced ADMA concentrations (SMD = -0.39, 95% CI -0.62 to -0.16, p = 0.001; moderate certainty of evidence). The extreme heterogeneity observed was substantially reduced in study subgroups of specific class and individual statins, regional areas, and analytical methods for ADMA concentrations. There was no publication bias. In sensitivity analysis, the corresponding SMD values were not substantially modified when individual studies were sequentially removed. Significant associations were observed, in meta-regression, between the SMD and publication year (t = -3.25, p = 0.003), but not baseline cholesterol concentrations. CONCLUSION Statin treatment significantly lowers ADMA concentrations. This effect is independent of baseline cholesterol. Prospective studies are required to determine whether ADMA-lowering mediates, at least partly, the protective effects of statins against atherosclerotic cardiovascular disease. (PROSPERO registration number: CRD42021275123).
-
2.
Polypill for cardiovascular disease prevention: Systematic review and meta-analysis of randomized controlled trials.
Mohamed, MG, Osman, M, Kheiri, B, Saleem, M, Lacasse, A, Alkhouli, M
International journal of cardiology. 2022;:91-98
Abstract
BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Although many pharmacological agents exist, drug compliance and therapeutic goal achievement continue to be suboptimal. This meta-analysis aims to study the effectiveness of polypills in controlling blood pressure, dyslipidemia and in reducing future cardiovascular events. METHODS We conducted a systematic search of electronic databases using pre-specified terms. Randomized clinical trials (RCT) comparing polypills (statin, antihypertensive agents, with or without aspirin) with the standard of care were included. Outcomes of interest were changes in [systolic blood pressure (SBP), diastolic blood pressure (DBP)] mmHg, [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C)] mg/dl, cardiovascular (CVD) mortality, and major adverse cardiovascular events (MACE). RESULTS A total of 18 RCTs with 26,483 participants were included. The population had 55% males, with a mean age of 61.8 ± 7 years, and a mean BMI of 26.7 ± 4.2 kg/m2. The mean follow-up was 15.0 ± 20 months. Compared with standard of care, polypill use was associated with a significant reduction of SBP (Mean Difference [MD] -6.39; [95%CI -9.21, -3.56] p < 0.001), DBP (MD -4.19, [95%CI -5.48, -2.89; p < 0.001], TC (MD -24.95, [95%CI -33.86, -16.04]; p < 0.001), and LDL-C (MD -27.92, [95%CI -35.39, -20.44]; p < 0.001). Polypill use was also associated with a significant reduction of CVD mortality (RR = 0.78; 95% CI (0.61, 0.99); P = 0.04) and MACE [RR = 0.76;95% CI (0.64, 0.91); P = 0.002]. CONCLUSION This meta-analysis showed that compared to standard of care, polypill use was associated with a significant reduction of SBP, DBP, TC, LDL-C, and a significant reduction in fatal and non-fatal cardiovascular events.
-
3.
The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis.
Liu, M, Fan, F, Zhang, Y, Li, J
European journal of clinical pharmacology. 2021;(3):349-357
-
-
Free full text
-
Abstract
PURPOSE Statin-induced myopathy (SIM) is the commonest reason for discontinuation of statin therapy. The aim of this present meta-analysis is to assess the relationship between glycine amidinotransferase gene (GATM) polymorphism and risk of SIM. METHODS MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched systematically for case-control studies investigating the relationship between GATM polymorphism and SIM. Retrieved articles were carefully reviewed and assessed according to the inclusion criteria. Associations were assessed in pooled data by calculating odds ratio with 95% confidence intervals. Subgroup analysis was performed according to comedications and severity of SIM. RESULTS Six studies with 707 cases and 2321 controls were included in this meta-analysis. GATM rs9806699 G>A was associated with decreased risk of SIM (OR = 0.80, 95% CI 0.68-0.94, P = 0.006). This association remained significant in the subgroup with fibrates or niacin excluded. However, the association of rs9806699 G>A with severe SIM was not significant. In addition, another two variations at GATM, rs1719247 C>T, and rs1346268 T>C were also associated with declined risk of SIM. CONCLUSIONS GATM polymorphism including rs9806699 G>A, rs1719247 C>T, and rs1346268 T>C may be protective factors of SIM. GATM rs9806699 G>A may only exert protective effect on mild SIM cases. Our meta-analysis indicates that GATM polymorphism may represent a pharmacogenomics biomarker for predicting incidence of SIM, which contributes to risk stratification and optimizing statin adherence.
-
4.
Statin use and new-onset of inflammatory bowel disease: A systematic review and meta-analysis of over ten million participants.
Bhagavathula, AS, Clark, C, Rahmani, J
European journal of pharmacology. 2021;:173750
Abstract
Statin therapy is used ubiquitously to reduce cholesterol levels, and recent studies have revealed statin use may be associated with a reduced risk of inflammatory bowel disease (IBD). A comprehensive assessment of the literature was performed to investigate whether statin use may influence the risk of new-onset IBD. We searched the PubMed/MEDLINE, Cochrane, Web of Science, and Scopus online databases, for articles published up to July 31, 2020. Hazard ratios (HR) with 95% confidence intervals (CI) were used. We identified five retrospective studies, with seven arms, comprising >10 million participants, consisting of 89,324 cases of IBD (statin users: 14,494 versus non-users: 74,830) detected during a mean follow-up of 8.6 years. Overall, statin use was associated with a reduced risk of new-onset IBD (HR = 0.81; 95% CI, 0.63 to 1.06; P = 0.129, I2 = 81.3%). Pooled results indicated a non-significant reduced risk of new-onset CD (HR = 0.94; 95% CI, 0.72 to 1.25; P = 0.684, I2 = 85.9%) and new-onset UC (HR = 0.89; 95% CI, 0.70 to 1.12; P = 0.306, I2 = 92.5%) with statin use. Statin use may confer a protective effect in reducing the risk of new-onset IBD. Indeed, this study provides novel and intriguing insights into a potential preventive agent for IBD.
-
5.
Meta-Analysis Comparing the Effect of Combined Omega-3 + Statin Therapy Versus Statin Therapy Alone on Coronary Artery Plaques.
Fan, H, Zhou, J, Yuan, Z
The American journal of cardiology. 2021;:15-24
Abstract
Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 μm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.
-
6.
The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jamialahmadi, T, Baratzadeh, F, Reiner, Ž, Simental-Mendía, LE, Xu, S, Susekov, AV, Santos, RD, Sahebkar, A
Mediators of inflammation. 2021;:9661752
Abstract
BACKGROUND Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. OBJECTIVE The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. METHODS PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. RESULTS Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I 2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I 2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I 2: 0%). CONCLUSION High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.
-
7.
Effects of atorvastatin on the insulin resistance in women of polycystic ovary syndrome: A systematic review and meta-analysis.
Chen, LL, Zheng, JH
Medicine. 2021;(24):e26289
-
-
Free full text
-
Abstract
BACKGROUND Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial. OBJECTIVE The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice. METHODS Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value. RESULTS Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD -0.06, 95% CI -0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD -1.84, 95% CI -3.06 to -0.62, P < .003). The homeostasis model assessment of insulin resistance (HOMA-IR) value showed significant decrease in the atorvastatin therapy compared to placebo (6 trials; SMD -4.12, 95% CI -6.00 to -2.23, P < .0001). In contrast to placebo, atorvastatin therapy did not decrease the BMI value significantly in PCOS patients (7 trials; SMD 0.12, 95% CI -0.07 to 0.31, P = .22). CONCLUSIONS Atorvastatin therapy can reduce insulin resistance in the treatment of patients with PCOS. In addition, further large-sample, multi-center RCTs are needed to identify these findings.
-
8.
Statin use and mortality in atrial fibrillation: A systematic review and meta-analysis of 100,287 patients.
Pastori, D, Baratta, F, Di Rocco, A, Farcomeni, A, Del Ben, M, Angelico, F, Violi, F, Pignatelli, P, Lip, GYH
Pharmacological research. 2021;:105418
Abstract
Statins are effective for reducing cardiovascular disease in patients at risk or with cardiovascular disease. The benefit of statin therapy on adverse cardiovascular outcomes in patients with non-valvular atrial fibrillation (AF) is not clear. We performed a systematic review and meta-analysis of studies retrieved from MEDLINE via PubMed and Cochrane (CENTRAL) database of studies investigating the efficacy of statins in AF patients. The principal endpoint was all-cause mortality. Other endpoints were cardiovascular mortality, ischemic stroke, composite endpoints and any bleeding. We included 14 studies (2 post-hoc analysis of randomized clinical trials, 8 prospective and 4 retrospective) with 100,287 AF patients, of whom 23,228 were on statins. The pooled hazard ratio (HR) for all-cause mortality was 0.59 (95 % Confidence Interval [CI] 0.54-0.65). This association was consistent by aging, sex and prevalent cardiovascular or cerebrovascular disease. and the beneficial effect was evident already after 12 months of therapy. The absolute risk reduction for all-cause mortality in patients treated with statins was 10 % (95 % CI 9-10). The pooled HR for statins against cardiovascular mortality was 0.75 (95 % CI 0.58-0.96). No association was found with other secondary endpoints. Regarding bleeding events, the pooled HR for statin use was 0.60 (95 % CI 0.48-0.76). Our meta-analysis shows that in AF patients, statin therapy was associated with a reduction in all-cause and cardiovascular mortality are reduced by 41 % and 25 %, respectively. Randomized clinical trials in AF patients are necessary, as well as clarity on AF-specific LDL cholesterol targets.
-
9.
Effects of Statins on Lipid Profile of Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials.
Huang, X, Jia, Y, Zhu, X, Zhang, Y, Jiang, L, Wei, X, Zhao, D, Zhao, X, Du, Y
BioMed research international. 2020;:9094543
Abstract
OBJECTIVE To assess the benefits of statins on lipid profile in kidney transplant recipients via a meta-analysis. METHODS We systematically identified peer-reviewed clinical trials, review articles, and treatment guidelines from PubMed, Embase, the Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), SinoMed (CBM), and Chongqing VIP databases from inception to April 2019. In the analysis, only randomized controlled clinical trials performed in human were included. RESULTS Eight articles were included in the analysis, involving 335 kidney transplant recipients who received statins and 350 kidney transplant patients as the control group. Results revealed that statins improved the lipid profile of kidney transplant recipients. Specifically, statin therapy significantly reduced total cholesterol and low-density lipoprotein cholesterol. However, it had no effects on high-density lipoprotein cholesterol and triglyceride levels. CONCLUSIONS The present study provides valuable knowledge on the potential benefits of statins in kidney transplant recipients. This meta-analysis shows that statin therapy modifies the lipid profile in this patient population.
-
10.
Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression.
Masson, W, Lobo, M, Siniawski, D, Molinero, G, Masson, G, Huerín, M, Nogueira, JP
Lipids in health and disease. 2020;(1):111
Abstract
BACKGROUND Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression. METHODS A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. RESULTS Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [- 4.0 mm3 (CI 95% -5.4 to - 2.6)]; I2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm3 and 1.1 mm3 regressions in TAV. CONCLUSION These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV. Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).